Gram-negative BacteraemiaPhase 4INVESTNCT05199324
Early Oral Switch for Uncomplicated Gram-negative Bacteraemia
A Phase 4 study testing Oral fluoroquinolones (most commonly, ciprofloxacin) or oral trimethoprim-sulfamethoxazole in people with Gram-negative Bacteraemia, run by Tan Tock Seng Hospital at 25 sites in 11 countries.
Trial summary
Current management of uncomplicated Gram-negative bacteraemia entails prolong intravenous (IV) antibiotic therapy with limited evidence to guide oral conversion. This trial aim to evaluate the clinical efficacy and economic impact of early switch to oral antibiotics (within 72 hours from index blood culture… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gram-negative Bacteraemia
- What is being tested?
- Oral fluoroquinolones (most commonly, ciprofloxacin) or oral trimethoprim-sulfamethoxazole
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 720 participants
- Where
- 25 sitesin 11 countries
- Study dates
- 3 Jun 2022to 23 Jul 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- One or more set(s) of blood cultures positive for Gram-negative bacteria (GNB) associated with evidence of infection
- Able to be randomised within 72 hours of index blood culture collection
- Age ≥18 years (≥21 in Singapore)
- Latest Pitt bacteraemia score <4
- Patient or legal representative is able to provide informed consent
Who cannot join
- Established uncontrolled focus of infection, including but not limited to:
- Undrained abdominal abscess, deep seated intra-abdominal infection and other unresolved abdominal sources requiring surgical intervention
- Central nervous system abscess (patients with focal neurology should have cranial CT prior to enrolment)
- Undrained moderate-to-severe hydronephrosis
- Complicated infections, including but not limited to:
- Necrotising fasciitis
Show all 28Show fewer
- Empyema
- Central nervous system infections and meningitis
- Endocarditis / endovascular infections
- Septic shock as defined by systolic blood pressure <90 or mean arterial pressure <70 mmHg despite adequate fluid resuscitation or need for inotropic/vasopressor support
- Polymicrobial bacteraemia involving Gram-positive pathogens or anaerobes (defined as either growth of 2 or more different microorganism species in the same blood culture, or growth of different species in 2 or more separate blood cultures within the same episode [<48 hours] and with clinical or microbiological evidence of the same source)
- Bacteraemia is due to a vascular catheter or intravascular materials (e.g. pacing wire, vascular graft) that cannot be removed
- Specific Gram-negative pathogens that cannot be effectively treated with fluoroquinolones or trimethoprim-sulfamethoxazole, including but not limited to, Burkholderia spp. and Brucella spp.
- Index GNB with resistance to fluoroquinolones AND trimethoprim-sulfamethoxazole
- Hypersensitivity to fluoroquinolones AND sulphur drugs as defined by history of rash, urticaria, angioedema, bronchospasm, circulatory collapse or significant adverse reaction following prior administration
- Unable to consume or absorb oral medications for any reason or unsuitable for ongoing IV therapy (e.g. no intravenous access)
- Severely immunocompromised in the opinion of the treating doctor, including but not limited to, medical conditions such as:
- Active leukaemia or lymphoma
- Aplastic anaemia
- Bone marrow transplant within two years of transplantation or transplants of longer duration still on immunosuppressive drugs or with graft-versus-host disease
- Congenital immunodeficiency
- HIV/AIDS with CD4 lymphocyte count <200
- Neutropenia or expected post-chemotherapy neutropenia within 14 days from the time of screening, defined as absolute neutrophil count < 500 cells/μL
- Women who are known to be pregnant or breast-feeding
- Treatment is not with intent to cure the infection (i.e. palliative care)
- Unable to collect patient's follow-up data for at least 30 days post-randomisation for any reason
- Treating doctor deems enrolment into the trial is not in the best interest of the patient
- Previous enrolment in this trial
Trial locations and contacts
25 sites in 11 countries.
25 sites in 11 countries
Singapore6 sites
National University Hospital
Singapore, Singapore, 119074
Singapore General Hospital
Singapore, Singapore, 169608
Tan Tock Seng Hospital
Singapore, Singapore, 308433
Changi General Hospital
Singapore, Singapore, 529889
Sengkang General Hospital
Singapore, Singapore, 544886
Ng Teng Fong General Hospital
Singapore, Singapore, 609606
Malaysia4 sites
Hospital Ampang
Ampang, 68000
Hospital Universiti Kebangsaan Malaysia
Kuala Lumpur, 56000
Universiti Malaya Medical Centre
Kuala Lumpur, 59100
Sungai Buloh Hospital
Sungai Buloh, 47000
Australia3 sites
Royal Melbourne Hospital
Melbourne, Victoria, 3050
Gold Coast University Hospital
Southport, Queensland, 4215
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
Italy3 sites
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola
Bologna, 40138
IRCCS Hospital San Raffaele
Milan, 20132
University Hospital of Pisa
Pisa, 56124
Israel2 sites
Rambam Hospital
Haifa, 3109601
Sheba Medical Center
Ramat Gan, 5262000
South Korea2 sites
Seoul National University Bandang Hospital
Seongnam-si, Gyeonggi-do, 13620
Samsung Medical Center
Soeul, 06351
Taiwan1 site
Taichung Veterans General Hospital
Taichung, Xitun District, 407219
Turkey (Türkiye)1 site
Medipol Mega University Hospital
Istanbul, 34214
About this study
Official title: Early Oral Step-down Antibiotic Therapy Versus Continuing Intravenous Therapy for Uncomplicated Gram-negative Bacteraemia (the INVEST Trial)
Current management of uncomplicated Gram-negative bacteraemia entails prolong intravenous (IV) antibiotic therapy with limited evidence to guide oral conversion. This trial aim to evaluate the clinical efficacy and economic impact of early switch to oral antibiotics (within 72 hours from index blood culture collection) versus continuing standard of care IV therapy (for at least another 24 hours post-randomisation) for clinically stable / non-critically ill inpatients with uncomplicated Gram-negative bacteraemia.
Read the detailed description
This is an international, multicentre, randomised controlled, open-label, phase IV, non-inferiority trial with a non-inferiority margin of 6%. Eligible participants must be clinically stable / non-critically ill inpatients over the age of 18 years old (in Singapore, 21 years and above) with uncomplicated Gram-negative bacteraemia. Randomisation into the intervention or standard arms will be performed with 1:1 allocation ratio according to a randomisation list prepared in advance using a secure online randomisation system. Randomisation will be stratified by country and random sequence will be generated using random permuted blocks of unequal length. Participants randomised to the intervention arm (within 72 hours from index blood culture collection) will be immediately converted to oral fluoroquinolones (most commonly, ciprofloxacin) or oral trimethoprim-sulfamethoxazole. In the event of microbiological or clinical failure of the oral antibiotic treatment, escalation to IV antibiotics may be initiated at any time point post-randomisation. Participants randomised to the standard arm will continue to receive an active IV therapy for at least another 24 hours post-randomisation. All the study drugs (and dosage) would be routinely used in clinical practice and will be ordered/dispensed from the hospital pharmacy as per site institutional practice. The recommended treatment duration by the study team is 7 days of active antibiotics (including empiric therapy), although treatment regimen may be longer than 7 days if clinically indicated. Participants may be discharged home or to outpatient parenteral antimicrobial therapy (OPAT) at any time post-randomisation.
- Conditions
- Gram-negative Bacteraemia
- Being tested
- Oral fluoroquinolones (most commonly, ciprofloxacin) or oral trimethoprim-sulfamethoxazole, Standard of care intravenous antibiotics (e.g. ceftriaxone, cefazolin)
- Keywords
- uncomplicated bacteraemia, gram-negative bacteria, early oral switch, fluoroquinolones, ciprofloxacin, trimethoprim-sulfamethoxazole, oral antibiotics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral fluoroquinolones (most commonly, ciprofloxacin) or oral trimethoprim-sulfamethoxazoleDrug
Also called Ciprofloxacin, Bactrim, Co-Trimoxazole
Clinically stable / non-critically ill inpatients with uncomplicated Gram-negative bacteraemia randomised to the intervention arm will immediately be switched to oral antibiotics (within 72 hours from index blood culture collection)
Standard of care intravenous antibiotics (e.g. ceftriaxone, cefazolin)Drug
Also called Rocephin, Kefzol
Clinically stable / non-critically ill inpatients with uncomplicated Gram-negative bacteraemia randomised to the standard arm will continue to receive an active intravenous antibiotic therapy for at least another 24 hours post-randomisation
| Study group | Role | What they receive |
|---|---|---|
| Early switch to oral antibiotic therapy | Experimental | The oral antibiotic options are fluoroquinolones (most commonly, ciprofloxacin) or trimethoprim-sulfamethoxazole. The recommended doses for patients with normal renal function would be ciprofloxacin 750 mg twice daily (if body weight ≥70 kg) or ciprofloxacin 500 mg twice daily (if body weight <70 kg) or trimethoprim-sulfamethoxazole 5 mg/kg (for trimethoprim component) every 12 hourly or trimethoprim-sulfamethoxazole (160 mg / 800 mg; double strength) two tablets twice daily. Doses may be adjusted in the setting of renal dysfunction. The recommended treatment duration by the study team is 7 days of active antibiotics (including empiric therapy), although treatment regimen may be longer than 7 days due to regimen extension or requirement for prolonged regimen as clinically indicated. Receives: Drug: Oral fluoroquinolones (most commonly, ciprofloxacin) or oral trimethoprim-sulfamethoxazole |
| Continuing intravenous antibiotic therapy | Active comparator | The intravenous antibiotics to be administered will be determined by the treating doctor according to what would be considered standard of care in the hospital site. Commonly used intravenous antibiotics (and doses) for treatment of Gram-negative bacteraemia include ceftriaxone 2 g daily or cefazolin 2 g three times daily. The recommended treatment duration by the study team is 7 days of active antibiotics (including empiric therapy), although treatment regimen may be longer than 7 days due to regimen extension or requirement for prolonged regimen as clinically indicated. Receives: Drug: Standard of care intravenous antibiotics (e.g. ceftriaxone, cefazolin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause mortality at day 30 post-randomisation
Percentage of all-cause mortality at day 30 from the time of randomisation
Measured: 30 days
Secondary outcomes (12)
All-cause mortality at day 14 and day 90 post-randomisation
Percentage of all-cause mortality at day 14 and day 90 from the time of randomisation
Measured: 14 days and 90 days, respectively
Duration of survival (in days) up to day 90 post-randomisation
Hazard rate of survival from the time of randomisation until day 90
Measured: 90 days
Number of days on IV antibiotic therapy in the total index hospitalisation until (i) hospital discharge and (ii) day 90
Median number of days on IV antibiotic therapy in the total index hospitalisation (including outpatient parenteral antibiotic therapy [OPAT]) for surviving participants from the time of randomisation until i) hospital discharge and ii) day 90
Measured: Up to 90 days
Number of days alive and free of antibiotics (i. for all antibiotics, and ii. for IV antibiotics) between the time of randomisation and day 90
Median total days alive and free from antibiotics (both oral and IV) for surviving participants; median total days alive and free from IV antibiotics for surviving participants; median proportion of days alive and free from antibiotics (both oral and IV) for surviving participants who discontinued the study; median proportion of days alive and free from IV antibiotics for surviving participants who discontinued the study; median proportion of days alive and free from antibiotics (both oral and IV) for non-surviving participants; and median proportion of days alive and free from IV antibiotics for non-surviving participants.
Measured: 90 days
Treatment-emergent adverse events from the time of randomisation until day 90
Percentage of participants with each treatment-emergent adverse event. Adverse events of special interest include Clostridioides difficile-associated diarrhoea, peripherally inserted central catheter and other central venous catheter complications (e.g. catheter-related bloodstream infection, catheter-related superficial or deep venous thrombosis/thrombophlebitis, catheter blockage, and exit site infection) requiring line removal during index hospitalisation (including OPAT), and liver function test abnormalities or acute kidney injury.
Measured: 90 days
Change in treatment strategy, either due to an adverse event or presumed lack of efficacy of treatment regimen, between the time of randomisation and day 30
Percentage of participants who experienced a change in treatment strategy (e.g. switch to IV antibiotics from allocated oral antibiotics or vice versa) between the time of randomisation and day 30 due to: i) an adverse event deemed by the doctor to be of sufficient severity to change treatment strategy, or ii) presumed lack of efficacy of treatment strategy according to the judgement of the doctor.
Measured: 30 days
Time (in days) to being discharged alive from the total index hospitalisation between the time of randomisation and day 90
Hazard rate of discharge alive from the total index hospitalisation (including OPAT and hospital-in-the-home) between the time of randomisation and day 90 (note: any death occurrence within 90 study days will be considered '90 days')
Measured: 90 days
Number of days alive and not in hospital (including OPAT) up to day 90 post-randomisation
Median number of days alive and not in hospital (including OPAT) between the time of randomisation and day 90
Measured: 90 days
Readmission or extended index hospitalisation between the time of randomisation and day 90
Percentage of participants who were readmitted or experienced extended index hospitalisation. Readmission is defined as a new hospitalisation for any cause or a return to ambulatory hospital services occurring after discharge from the index hospitalisation. Extended index hospitalisation is defined as >14 days of hospital length of stay starting from the day of randomisation.
Measured: 90 days
Health-related quality of life (EQ-5D descriptive system) on the day of screening (baseline), on the day of end of treatment, and on day 90 post-randomisation
EQ-5D-5L consists of EQ-5D descriptive system and EQ visual analogue scale (EQ VAS). The descriptive system encompasses five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each of which has 5-level scale: no problems, slight problems, moderate problems, severe problems, and extreme problems. Participants will be asked to indicate their health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions will be combined into a 5-digit number that describes the participant's health state (e.g. 11211). The health state will then be converted into a utility index score using country specific value set, where 1 = full health and 0 = death. The utility index score can fall below 0 in culture which deems a health state is "worst than death".
Measured: 90 days
Health-related quality of life (EQ visual analogue scale) on the day of screening (baseline), on the day of end of treatment, and on day 90 post-randomisation
EQ-5D-5L consists of EQ-5D descriptive system and EQ visual analogue scale (EQ VAS). The EQ VAS records the participant's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS will be used as a quantitative measure of health outcome that reflects the participant's own judgement, where 0 indicates the worst health imaginable and 100 indicates the best health imaginable.
Measured: 90 days
Health economic evaluation up to day 90 post-randomisation
Health economic evaluation includes calculation of estimated total healthcare cost (from healthcare system and patient perspective) up to day 90 post-randomisation. The health economic evaluation component of this study will be performed for participating sites in Singapore and Malaysia only. Results of the health economic evaluation will be published separately from the main trial results manuscript.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2022
- Study start3 Jun 2022
- Primary completion24 May 2026
- Study completion23 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gram-negative BacteraemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 720 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tan Tock Seng Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Singapore Clinical Research Institute, Consorzio per Valutazioni Biologiche e Farmacologiche
- Responsible party
- Sponsor
- Investigators
- David Lye, MBBS, Principal investigator, Tan Tock Seng Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05199324
- Sponsor's protocol ID
- DSRB 2021/00764
- Acronym
- INVEST
- Status last verified
- Aug 2026
- First submitted
- 21 Dec 2021
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Lee IR, Tong SYC, Davis JS, Paterson DL, Syed-Omar SF, Peck KR, Chung DR, Cooke GS, Libau EA, Rahman SBA, Gandhi MP, Shi L, Zheng S, Chaung J, Tan SY, Kalimuddin S, Archuleta S, Lye DC. Early oral stepdown antibiotic therapy versus continuing intravenous therapy for uncomplicated Gram-negative bacteraemia (the INVEST trial): study protocol for a multicentre, randomised controlled, open-label, phase III, non-inferiority trial. Trials. 2022 Jul 19;23(1):572. doi: 10.1186/s13063-022-06495-3.
PubMed 35854360
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Oral Step-down Antibiotic Therapy Versus Continuing Intravenous Therapy for Uncomplicated Gram-negative Bacteraemia (the INVEST Trial)
- ClinicalTrials.gov ID
- NCT05199324
- Acronym / sponsor ID
- INVEST / DSRB 2021/00764
- Conditions
- Gram-negative Bacteraemia
- Keywords
- uncomplicated bacteraemia, gram-negative bacteria, early oral switch, fluoroquinolones, ciprofloxacin, trimethoprim-sulfamethoxazole, oral antibiotics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 720 participants (actual)
- Lead sponsor
- Tan Tock Seng HospitalUniversity, hospital or other
- Collaborators
- Singapore Clinical Research Institute, Consorzio per Valutazioni Biologiche e Farmacologiche
- Study start
- 3 Jun 2022 (actual)
- Primary completion
- 24 May 2026 (actual)
- Study completion
- 23 Jul 2026 (actual)
- First posted
- 20 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Current management of uncomplicated Gram-negative bacteraemia entails prolong intravenous (IV) antibiotic therapy with limited evidence to guide oral conversion. This trial aim to evaluate the clinical efficacy and economic impact of early switch to oral antibiotics (within 72 hours from index blood culture collection) versus continuing standard of care IV therapy (for at least another 24 hours post-randomisation) for clinically stable / non-critically ill inpatients with uncomplicated Gram-negative bacteraemia.
Detailed description
This is an international, multicentre, randomised controlled, open-label, phase IV, non-inferiority trial with a non-inferiority margin of 6%. Eligible participants must be clinically stable / non-critically ill inpatients over the age of 18 years old (in Singapore, 21 years and above) with uncomplicated Gram-negative bacteraemia. Randomisation into the intervention or standard arms will be performed with 1:1 allocation ratio according to a randomisation list prepared in advance using a secure online randomisation system. Randomisation will be stratified by country and random sequence will be generated using random permuted blocks of unequal length. Participants randomised to the intervention arm (within 72 hours from index blood culture collection) will be immediately converted to oral fluoroquinolones (most commonly, ciprofloxacin) or oral trimethoprim-sulfamethoxazole. In the event of microbiological or clinical failure of the oral antibiotic treatment, escalation to IV antibiotics may be initiated at any time point post-randomisation. Participants randomised to the standard arm will continue to receive an active IV therapy for at least another 24 hours post-randomisation. All the study drugs (and dosage) would be routinely used in clinical practice and will be ordered/dispensed from the hospital pharmacy as per site institutional practice. The recommended treatment duration by the study team is 7 days of active antibiotics (including empiric therapy), although treatment regimen may be longer than 7 days if clinically indicated. Participants may be discharged home or to outpatient parenteral antimicrobial therapy (OPAT) at any time post-randomisation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early switch to oral antibiotic therapy | Experimental | Drug: Oral fluoroquinolones (most commonly, ciprofloxacin) or oral trimethoprim-sulfamethoxazoleThe oral antibiotic options are fluoroquinolones (most commonly, ciprofloxacin) or trimethoprim-sulfamethoxazole. The recommended doses for patients with normal renal function would be ciprofloxacin 750 mg twice daily (if body weight ≥70 kg) or ciprofloxacin 500 mg twice daily (if body weight <70 kg) or trimethoprim-sulfamethoxazole 5 mg/kg (for trimethoprim component) every 12 hourly or trimethoprim-sulfamethoxazole (160 mg / 800 mg; double strength) two tablets twice daily. Doses may be adjusted in the setting of renal dysfunction. The recommended treatment duration by the study team is 7 days of active antibiotics (including empiric therapy), although treatment regimen may be longer than 7 days due to regimen extension or requirement for prolonged regimen as clinically indicated. |
| Continuing intravenous antibiotic therapy | Active comparator | Drug: Standard of care intravenous antibiotics (e.g. ceftriaxone, cefazolin)The intravenous antibiotics to be administered will be determined by the treating doctor according to what would be considered standard of care in the hospital site. Commonly used intravenous antibiotics (and doses) for treatment of Gram-negative bacteraemia include ceftriaxone 2 g daily or cefazolin 2 g three times daily. The recommended treatment duration by the study team is 7 days of active antibiotics (including empiric therapy), although treatment regimen may be longer than 7 days due to regimen extension or requirement for prolonged regimen as clinically indicated. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- One or more set(s) of blood cultures positive for Gram-negative bacteria (GNB) associated with evidence of infection
- Able to be randomised within 72 hours of index blood culture collection
- Age ≥18 years (≥21 in Singapore)
- Latest Pitt bacteraemia score <4
- Patient or legal representative is able to provide informed consent
Key exclusion criteria (28 listed)
- Established uncontrolled focus of infection, including but not limited to:
- Complicated infections, including but not limited to:
- Septic shock as defined by systolic blood pressure <90 or mean arterial pressure <70 mmHg despite adequate fluid resuscitation or need for inotropic/vasopressor support
- Polymicrobial bacteraemia involving Gram-positive pathogens or anaerobes (defined as either growth of 2 or more different microorganism species in the same blood culture, or growth of different species in 2 or more separate blood cultures within the same episode [<48 hours] and with clinical or microbiological evidence of the same source)
- Bacteraemia is due to a vascular catheter or intravascular materials (e.g. pacing wire, vascular graft) that cannot be removed
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral fluoroquinolones (most commonly, ciprofloxacin) or oral trimethoprim-sulfamethoxazoleAlso: Ciprofloxacin, Bactrim, Co-TrimoxazoleClinically stable / non-critically ill inpatients with uncomplicated Gram-negative bacteraemia randomised to the intervention arm will immediately be switched to oral antibiotics (within 72 hours from index blood culture collection) | Drug | Early switch to oral antibiotic therapy |
| Standard of care intravenous antibiotics (e.g. ceftriaxone, cefazolin)Also: Rocephin, KefzolClinically stable / non-critically ill inpatients with uncomplicated Gram-negative bacteraemia randomised to the standard arm will continue to receive an active intravenous antibiotic therapy for at least another 24 hours post-randomisation | Drug | Continuing intravenous antibiotic therapy |
Primary outcome
All-cause mortality at day 30 post-randomisation
Time frame: 30 days
Percentage of all-cause mortality at day 30 from the time of randomisation
12 secondary outcomes
All-cause mortality at day 14 and day 90 post-randomisation
Time frame: 14 days and 90 days, respectively
Duration of survival (in days) up to day 90 post-randomisation
Time frame: 90 days
Number of days on IV antibiotic therapy in the total index hospitalisation until (i) hospital discharge and (ii) day 90
Time frame: Up to 90 days
Number of days alive and free of antibiotics (i. for all antibiotics, and ii. for IV antibiotics) between the time of randomisation and day 90
Time frame: 90 days
Treatment-emergent adverse events from the time of randomisation until day 90
Time frame: 90 days
Change in treatment strategy, either due to an adverse event or presumed lack of efficacy of treatment regimen, between the time of randomisation and day 30
Time frame: 30 days
Time (in days) to being discharged alive from the total index hospitalisation between the time of randomisation and day 90
Time frame: 90 days
Number of days alive and not in hospital (including OPAT) up to day 90 post-randomisation
Time frame: 90 days
Readmission or extended index hospitalisation between the time of randomisation and day 90
Time frame: 90 days
Health-related quality of life (EQ-5D descriptive system) on the day of screening (baseline), on the day of end of treatment, and on day 90 post-randomisation
Time frame: 90 days
Health-related quality of life (EQ visual analogue scale) on the day of screening (baseline), on the day of end of treatment, and on day 90 post-randomisation
Time frame: 90 days
Health economic evaluation up to day 90 post-randomisation
Time frame: 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2026.
- Background: PubMed 35854360Lee IR, Tong SYC, Davis JS, Paterson DL, Syed-Omar SF, Peck KR, Chung DR, Cooke GS, Libau EA, Rahman SBA, Gandhi MP, Shi L, Zheng S, Chaung J, Tan SY, Kalimuddin S, Archuleta S, Lye DC. Early oral stepdown antibiotic therapy versus continuing intravenous therapy for uncomplicated Gram-negative bacteraemia (the INVEST trial): study protocol for a multicentre, randomised controlled, open-label, phase III, non-inferiority trial. Trials. 2022 Jul 19;23(1):572. doi: 10.1186/s13063-022-06495-3.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Lye, MBBS principal investigator
Tan Tock Seng Hospital
25 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Oral fluoroquinolones (most commonly, ciprofloxacin) or oral trimethoprim-sulfamethoxazole in people with Gram-negative Bacteraemia, run by Tan Tock Seng Hospital at 25 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in Singapore, Malaysia, Australia, Italy, Israel and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause mortality at day 30 post-randomisation (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05199324, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2026.